1. Field of the Invention
This invention relates to 2',3'-dideoxy-4'-thioribonucleosides and to their use as antiviral, especially anti-AIDS agents.
2. Description of the Related Art
2',3'-Dideoxynucleosides are known to be potent and selective agents for the treatment of AIDS. Within this series of compounds, dideoxycytidine, dideoxyinosine and AZT (3'-azido-3'-deoxythymidine) have been found to be particularly potent. However, each of these compounds produce undesirable side effects.
Thionucleoside analogues of 2',3'-dideoxynucleosides and their use as antiviral agents have not been previously reported.
Several 4'-thionucleosides have been reported in the literature. Reist, et al, J. Am. Chem. Soc., 86, 5658 (1964) disclose L and D forms of 4'-thioriboadenosine. Biological effects of 4'-thioriboadenosine are described in Miura, et al in Purine and Pyrimidine Metabolism in Man, V, Part B, (Plenum Publishing Corp., 1986) p. 667. Richie, et al, Can. J. Chem., 56, 794 (1977) disclose the synthesis of 9-(3-deoxy-4-thio-.beta.-D-erythro-pentofuranosyl)adenine (4'-thiocordycepin). Reist, et al, J. Org. Chem., 33, 189 (1968) describe the synthesis of adenine nucleosides of 4-thio-D-xylose and 4-thio-D-arabinose. Ototani, et al. J. Med. Chem., 17, 535 (1974) disclose the preparation and antitumor activity of 4'-thio-1-.beta.-D-arabinofuranosylcytosine and 2,2'-anhydro-4'-thio-1-.beta.-D-arabinofuranosylcytosine hydrochloride.
Fu, et al, J. Org. Chem., 41, 3831 (1976) disclose a method for the preparation of anomeric methyl-2-deoxy-4-thio-D-erythro-pentofuranosides and suggest that the furanosides could be used as precursors for the synthesis of 2'-deoxy-4'-thionucleosides.